Real-World Research in Diabetes Care and Protocols for Patient Privacy

2001 to $192.2 billion. Drug price inflation for existing drugs was 4% in 2002, twice the inflation rate in the general economy and more than one third of the total 11.7% increase in drug spending. Utilization as measured by the volume of prescriptions accounted for less than 40% of the increase in total sales. Drug “mix,” defined as the use of newer, higher-cost drugs, accounted for the balance of the drug cost trend in 2002. In other words, inflation in prices of existing drugs, utilization, and the drug “mix” each accounted for about one third of the total increase in prescription drug spending in 2002. Data from Verispan Scott-Levin for community pharmacy sales in calendar year 2002 show a more remarkable influence of price versus utilization in prescription drug sales. These data, based on prescriptions dispensed in 36,000 chain and independent pharmacies, mass-merchandisers, deep-discounters, and food stores, showed a 10% increase in prescription drug sales in 2002 to $166.66 billion, contributed 95% by price and about 5% by utilization. The average prescription price increased by 9.5% to $54.57 in 2002, and volume increased 0.4% to 3.054 billion prescriptions. Yet, the commonly accepted measure of utilization of prescription drugs, the prescription dispensed, has flaws, and the drug industry position, as presented by NPC and PhRMA, has merit in this regard. Unreported in the summary data for community pharmacy is the “size” of the average prescription as measured in days of therapy. Second, the relative growth in mailorder pharmacy sales in the United States over the last decade has contributed to growth in the size of the average prescription as measured in days of therapy. The customary mail-order prescription is nearly 3 times the size of the average prescription dispensed by community pharmacy, and a more precise measure of “utilization” would appear to be number of days of therapy rather than the number of prescriptions. At the least, this alternate measure of days of therapy would provide additional information about the trend of increased utilization of prescription drugs. Mail-order pharmacy accounted for about 120 million prescriptions and $8.5 billion in sales in 1995, or about 10% of the total pharmaceutical market. Mail-order pharmacy had an average annual growth rate of 20% over the 8-year period ended June 30, 2001, accounting for 16% of all prescription drug dollars in 2001. Data from IMS Health showed that mail-order pharmacy accounted for 17% of the prescription drug market in calendar year 2001 as measured by “retail” pharmacy sales (versus manufacturer sales). This growth in mail-order pharmacy as a percentage of total “retail” pharmacy sales would cause the prescription as a measure of utilization to understate the actual increase in utilization of prescription drugs and as a percentage of the total increase in prescription drug spending in the United States. The proliferation of generic drug alternatives in the treatment of depression, heartburn, hypertension, and other important therapeutic categories increases the opportunities for managed care pharmacy to blunt the cost trend in prescription drugs. Overall, much of the opportunity appears to be unfulfilled. For example, the top 2 drugs by total spending in 2002 were atorvastatin at $6.1 billion and simvastatin at $4.2 billion, up 19% and 16% from 2001, respectively. Both are brand drugs for treating dyslipidemia, a condition treated effectively in most patients by generic lovastatin at about 75% to 85% discount to the cost of the brand drug alternatives. Two of the other top 10 drugs in 2002 were sertraline at $2.5 billion and paroxetine at $2.3 billion, up 14% and 11% from 2001, respectively. These 2 drugs are therapeutic alternatives to generic fluoxetine, which has a managed care price about 90% less than sertraline or paroxetine. Stated in terms of population health, generic fluoxetine can treat about 10 patients with depression for the same managed care cost as treating 1 patient with either sertraline or paroxetine. Generic lovastatin can treat about 5 patients with dyslipidemia for the same managed care cost as 1 patient treated with simvastatin and about 4 patients with dyslipidemia for each patient treated with atorvastatin.

was 4% in 2002, twice the inflation rate in the general economy and more than one third of the total 11.7% increase in drug spending. Utilization as measured by the volume of prescriptions accounted for less than 40% of the increase in total sales. Drug "mix," defined as the use of newer, higher-cost drugs, accounted for the balance of the drug cost trend in 2002. In other words, inflation in prices of existing drugs, utilization, and the drug "mix" each accounted for about one third of the total increase in prescription drug spending in 2002.
Data from Verispan Scott-Levin for community pharmacy sales in calendar year 2002 show a more remarkable influence of price versus utilization in prescription drug sales. These data, based on prescriptions dispensed in 36,000 chain and independent pharmacies, mass-merchandisers, deep-discounters, and food stores, showed a 10% increase in prescription drug sales in 2002 to $166.66 billion, contributed 95% by price and about 5% by utilization. 12 The average prescription price increased by 9.5% to $54.57 in 2002, and volume increased 0.4% to 3.054 billion prescriptions.
Yet, the commonly accepted measure of utilization of prescription drugs, the prescription dispensed, has flaws, and the drug industry position, as presented by NPC and PhRMA, has merit in this regard. Unreported in the summary data for community pharmacy is the "size" of the average prescription as measured in days of therapy. Second, the relative growth in mailorder pharmacy sales in the United States over the last decade has contributed to growth in the size of the average prescription as measured in days of therapy. The customary mail-order prescription is nearly 3 times the size of the average prescription dispensed by community pharmacy, and a more precise measure of "utilization" would appear to be number of days of therapy rather than the number of prescriptions. At the least, this alternate measure of days of therapy would provide additional information about the trend of increased utilization of prescription drugs. 13 Mail-order pharmacy accounted for about 120 million prescriptions and $8.5 billion in sales in 1995, or about 10% of the total pharmaceutical market. 14 Mail-order pharmacy had an average annual growth rate of 20% over the 8-year period ended June 30, 2001, accounting for 16% of all prescription drug dollars in 2001. 15 Data from IMS Health showed that mail-order pharmacy accounted for 17% of the prescription drug market in calendar year 2001 as measured by "retail" pharmacy sales (versus manufacturer sales). 16 This growth in mail-order pharmacy as a percentage of total "retail" pharmacy sales would cause the prescription as a measure of utilization to understate the actual increase in utilization of prescription drugs and as a percentage of the total increase in prescription drug spending in the United States.
The proliferation of generic drug alternatives in the treatment of depression, heartburn, hypertension, and other important therapeutic categories increases the opportunities for managed care pharmacy to blunt the cost trend in prescription drugs. Overall, much of the opportunity appears to be unfulfilled. For example, the top 2 drugs by total spending in 2002 were atorvastatin at $6.1 billion and simvastatin at $4.2 billion, up 19% and 16% from 2001, respectively. Both are brand drugs for treating dyslipidemia, a condition treated effectively in most patients by generic lovastatin at about 75% to 85% discount to the cost of the brand drug alternatives. Two of the other top 10 drugs in 2002 were sertraline at $2.5 billion and paroxetine at $2.3 billion, up 14% and 11% from 2001, respectively. These 2 drugs are therapeutic alternatives to generic fluoxetine, which has a managed care price about 90% less than sertraline or paroxetine. Stated in terms of population health, generic fluoxetine can treat about 10 patients with depression for the same managed care cost as treating 1 patient with either sertraline or paroxetine. Generic lovastatin can treat about 5 patients with dyslipidemia for the same managed care cost as 1 patient treated with simvastatin and about 4 patients with dyslipidemia for each patient treated with atorvastatin.

■■ Real-World Research in Diabetes Care and Protocols for Patient Privacy
Two articles in this issue of the Journal derive from research in Veteran Affairs (VA) medical centers. Aside from the obvious predominance of males in these study populations, readers might also note the possibility of alternate explanations for the study findings in the effectiveness research in diabetes care by Duckworth, Marcelli, Padden, et al., using combination glyburide-metformin versus separate formulations of metformin and sulfonylurea. 17 In this pre/post study of patients switched from separate sulfonylurea and metformin to combination glyburidemetformin, there was a significant increase in (a) the number of patients who received insulin (on separate sulfonylura and metformin), from 5 (6.9%) in the preperiod to 19 (26.4%; P=0.0001) in the postperiod; (b) the number of patients who received additional oral antidiabetic agents, from 6 (8.3%) in the preperiod to 15 (20.8%; P=0.04) in the postperiod; and (c) the mean dose of metformin, from 1,607 mg in the preperiod to 1,750 mg in the post period (P=0.02). These factors create alternative explanations for the 0.6% improvement in hemoglobin A1C (P=0.002) at a mean follow-up of 196 days after the switch to combination glyburide-metformin tablets.
This study of combination glyburide-metformin suggests that there may be some synergy in the formulation of the combination product that is not explained by the simple addition of the 2 products, noting the possible alternate explanations for the findings. Also, there was a remarkable increase in the number of patients who experienced clinically significant hypoglycemia in the postswitch period, on the combination glyburide-metformin product. Eight patients experienced clinically significant hypoglycemia in the postperiod on the combination product versus 3 patients who experienced hypoglycemia in the preswitch period. This outcome may be related more to the significant increase in the number of patients who received concomitant insulin in the postswitch period rather than being attributable to the combination glyburide-metformin product. These 2 studies in VA medical centers, the study by Till, Voris, and Traywick and the study by Duckworth, Marcelli, Padden, et al., are published at a time when the VA is undergoing a thorough review of its medical research protocols. Results released in mid-March 2003 of investigations performed by the VA inspector general showed that "one or more patients" died due to falsified data at one VA research site, another patient received an overdose of a drug under study at a separate site, and there were 2 instances in 2 other VA medical centers in which a researcher did not have proper credentials and another in which an ethics board did not meet "even minimal standards" for safeguarding patients. 18 The VA conducts more than 15,000 research studies involving about 150,000 patients in a program that will cost $1.3 billion in fiscal year 2003. The VA was conducting a 90-day review of its clinical research practices at the 115 VA medical centers throughout the United States, a review process that was expected to be completed by early June 2003. The 90-day review was ordered by a memo signed by 2 deputy undersecretaries for health that was dated March 6, 2003, and warned that principal researchers at the VA centers "will be held responsible for ethical breaches in the conduct of their research." 19 Till, Voris, and Traywick noted in their article in this issue of the Journal that according to the research protocol at their VA institution, a code was assigned to each patient' s record to ensure patient confidentiality by blinding researchers to actual patient names. The VA policy on identifying patients is based on the U.S. Code of Federal Regulations (CFR) 46.101(b)(4), that says: "(4) …the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects." This language is consistent with the "final rule" published February 20, 2003, to implement the patient privacy and security standards of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 20 Patient records that are de-identified are no longer protected health information. HIPAA rules regarding the approval of research by a review board and confidentiality and privacy rights for access to medical records are covered in the Privacy Rule. 21 Also in this issue of the Journal, Hall, Summers, and Obenchain argue that the higher drug product cost for human insulin lispro (Humalog, Lilly), similar to human insulin aspart (Novolog, Novo Nordisk), is offset by apparent savings in other medical costs. This is a worthwhile debate, and the argument is of great interest to managed care pharmacists even if the extant study findings do not seem to be compelling to some observers; i.e., are short-term savings in hospital costs predictable from the use of human insulin lispro versus regular human insulin? Human insulin lispro commands a higher price (direct drug cost) of more than 2 times the price of regular human insulin because it provides additional benefits to users in the form of greater flexibility in dosing associated with its very rapid onset of action, making it possible to be injected immediately before meals. To noninsulin users, this may seem a minor point, but the faster onset of action reduces some of the demand made on patients with type 1 diabetes mellitus, and those with type 2 disease who require insulin, that stem from the incessant need for careful meal planning and timing of insulin administration. Numerous clinical studies have shown significant improvements in postprandial glycemic control and some evidence of reduced rates of severe or nocturnal hypoglycemia compared to conventional human insulin. 22 Quality-of-life studies show consistent preferences by patients for and increased treatment satisfaction with insulin lispro over regular human insulin, as measured by the diseasespecific Diabetes Treatment Satisfaction Questionnaire 23 and the more general health-related quality-of-life instruments. 24 Readers may find additional guidance regarding effective methods for managing diabetes care and avoiding adverse events in the supplement to this issue of the Journal. 25

■■ JMCP Award for Excellence
The JMCP Award for Excellence was created in 2002 to recognize the best article published each year in JMCP according to criteria that included originality, scientific merit, timeliness of the topic, relevance to managed care pharmacy, quality of the writing, and the potential impact on the profession or knowledge of managed care pharmacists. 26 The inaugural award was presented in April 2003 to Doctors Michael Gee, Noelle Hasson, Terri Hahn, and Russell Ryono for their research in the management of dyslipidemia among patients at a Veterans Affairs medical center in northern California. 27 The article by Gee, Hasson, Hahn, and Ryono reported research that measured clinical, service, and cost outcomes of pharmacist interventions with managed care patients. Conducted prior to the market introduction of generic lovastatin, the researchers found that tablet splitting of hydroxymethylglutaryl-CoA reductase inhibitor (HMG) drugs was associated with favorable clinical (laboratory) outcomes (i.e., a statistically significant, but perhaps not practically significant, decrease in low-density lipoprotein [LDL] after tablet splitting and favorable compliance with tablet splitting) and humanistic-service outcomes (patient satisfaction) while creating the opportunity to treat nearly twice as many patients for the same cost.